Unexplained Hyperthyrotropinemia: A Biochemical and Clinical Challenge

Laura Croce; Spyridon Chytiris; Francesca Coperchini; Giovanni Ferraro; Linda Minelli; Antonella Navarra; Flavia Magri; Luca Chiovato; Pierpaolo Trimboli; Mario Rotondi

doi:10.3390/jcm12082934

Unexplained Hyperthyrotropinemia: A Biochemical and Clinical Challenge

J Clin Med. 2023 Apr 18;12(8):2934. doi: 10.3390/jcm12082934.

Authors

Laura Croce^{1

2}, Spyridon Chytiris², Francesca Coperchini², Giovanni Ferraro³, Linda Minelli⁴, Antonella Navarra³, Flavia Magri^{1

2}, Luca Chiovato^{1

2}, Pierpaolo Trimboli^{5

6}, Mario Rotondi^{1

2}

Affiliations

¹ Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
² Unit of Endocrinology, Laboratory for Endocrine Disruptors, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy.
³ Laboratory Service, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy.
⁴ Unit of Internal Medicine, Medical-Oncologic Department, ASST Lodi, 26900 Lodi, Italy.
⁵ Clinic for Endocrinology and Diabetology, Lugano Regional Hospital, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland.
⁶ Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), 6900 Lugano, Switzerland.

Abstract

Background: A raised serum TSH in the absence of a clear etiology, or "unexplained hyperthyrotropinemia" (UH), can be challenging for clinicians. The aim of the present study was to evaluate potential strategies aimed at a clinical and biochemical characterization of UH patients.

Methods: We compared 36 patients with UH with a control group of 14 patients with chronic autoimmune thyroiditis (CAT) and subclinical hypothyroidism. The two groups were compared in terms of the following: (i) the rate of normalization of TSH after repeating with another assay; (ii) the rate of normalization of TSH over time with the same assay; (iii) the reduction in TSH after precipitation with polyethilenglycole (PEG); and (iv) free thyroxine (FT4) levels.

Results: Similar TSH levels were observed in UH [5.65 (5.21-6.37)] and CAT [5.62 (5.17-8.50)] (p = 0.489). TSH measurement with another assay method showed a normal TSH value in 41.9% of UH vs. 46.1% of CAT patients (p = 0.797). After repeating the TSH measurement in time with the same assay method, an increased TSH value was confirmed in all cases, in both groups (0% in the UH group vs. 0% in the CAT group, p = 1.000). TSH recovery after PEG precipitation was similar in the two groups (% precipitable post-PEG: 68.75 ± 3.14 in UH vs. 68.67 ± 7.18 in CAT, p = 0.960). FT4 levels were similar in the two groups (FT4 1.02 ± 0.20 ng/dl in UH vs. 1.00 ± 0.20 ng/dl in CAT, p = 0.789).

Conclusions: The results do not support the concept that laboratory interferences are more frequent in UH patients, suggesting that patients with UH should be managed in the same way as patients with CAT until proven otherwise.

Keywords: laboratory interference; macro-TSH; subclinical hypothyroidism; unexplained hyperthyrotropinemia.

Grants and funding

This work was partially supported by the ‘Ricerca Corrente’ funding scheme of the Ministry of Health Italy. The Author F.C. was supported by the Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for proposals No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU; Award Number: Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title “ON Foods-Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods”.